WASHINGTON (Dispatches)-A new method allows researchers to systematically identify specialized proteins called 'nuclesome displacing factors' that unpack DNA inside the nucleus of a cell, making the usually dense DNA more accessible for gene expression and other functions.
"Our genome is very compact, which means there is an accessibility issue," said Lu Bai, assistant professor of biochemistry and molecular biology and of physics at Penn State and senior author of the study. "A variety of proteins need to access DNA to copy its information into the RNA that will eventually be used to make proteins, but DNA is tightly wrapped around proteins called histones that are then packed into bead-like structures called nucleosomes. These tightly packed nucleosomes make it hard for other proteins to bind.
"To solve this problem, cells use what we call 'nucleosome-displacing factors' to invade the condensed DNA and open it up. Until this study, we lacked a general method to screen for these factors and evaluate them."
Nucleosome-displacing factors are a special kind of transcription factor, proteins that bind to short, specific sequences of DNA called binding sites to control gene expression. They are also known as pioneer factors in animal cells. The researchers developed a fast, inexpensive "high-throughput" method to screen and categorize large numbers of transcription factors based on their ability to displace nucleosomes. The method artificially incorporates transcription factor binding sites into the nucleosomes and examines which factors are capable of reducing the presence of nucleosomes.
The researchers identified both new and previously known nucleosome-displacing factors. These factors, particularly those that strongly deplete nucleosomes, tend to be highly abundant in the nucleus and bind very tightly to DNA.